Design, Synthesis, Docking Studies and Biological Activities Novel 2,3- Diaryl-4-Quinazolinone Derivatives as Anti-HIV-1 Agents

Abstract

Background: Although major efforts have been devoted to the effective treatment of HIV-1 infection, it has remained one of the leading causes of deaths around the world. So, development of anti-HIV-1 agents featuring novel structure is essential. Objective: To synthesize novel quinazolinone derivatives and evaluate their anti-HIV-1 activity. Method: In this study, we designed and synthesized a series of novel 2,3-diaryl-4-quinazolinone derivatives using a one-pot multicomponent reaction. Then, the resulting derivatives were evaluated for anti-HIV-1 activity using Hela cell-based single-cycle replication assay. Results: Most of the compounds showed efficacy against HIV-1 replication and the compound 9c exhibited the highest activity with EC50 value of 37 μM. Docking studies indicated that synthesized compounds can interact with the key residues of the HIV-1 integrase active site. Binding of the most active compound was consistent with the HIV-1 integrase inhibitors. Conclusion: Based on our results, these derivatives represent novel lead compounds for the development of new promising anti-HIV-1 agents.

Novel 2-(Diphenylmethylidene) Malonic Acid Derivatives as Anti-HIV Agents: Molecular Modeling, Synthesis and Biological Evaluation

“…Docking results revealed that all compounds accommodated well in the binding sites with binding energies ranging from -5.7 to -10.1 kcal/mol ( Figure 6 ). Most compounds demonstrated binding energies similar to the reference molecules, and in some compounds ( 8 , 9 , 11 , 16 ), the binding energies to the RT enzyme were even better than that of the reference molecule. Compounds 4 and 16 indicated high binding affinities for HIV PR and RT binding sites with ∆G values of -8.4 and -10.1 kcal/mol, respectively.…”

“…That is why it is still crucial to find new ways to effectively combat the disease. The currently used highly active antiretroviral therapy (HAART) is reported as the most effective anti-HIV drug regimen that significantly decreases HIV viral load, changing AIDS from a rapidly lethal condition to a manageable chronic disease (5)(6)(7)(8). Nevertheless, HAART benefits are still overshadowed by problems such as drug-drug interactions, adverse drug reactions, poor patient adherence, high costs, and the emergence of drug-resistant viral strains (9)(10)(11).…”

A green synthesis of pyrimido[4,5-b]quinolines and pyrido[2,3-d]pyrimidines via a mechanochemical approach

“…34–37 Another N-heterocyclic scaffold, namely pyrido[2,3- d ]pyrimidine is also an important compound with a broad range of biological activities and pharmaceutical profiles, such as being an anti-HIV agent; an anti-allergic agent, ramastine; and a human leukocyte elastase inhibitor, SSR69071. 38–40…”

Synthesis and evaluation of in vitro biological activity of new series of quinazolinone and benzoxazinone derivatives

“…Also, functionalized quinazolines possess diverse biological, and pharmaceutical activities as antibacterial [14], antioxidant [15], antiviral [16], anti-HIV [17], anticonvulsant [18], anti-obesity [19], antituberculosis [20], inflammatory [21], analgesic [22], anti-diabetes [23], anti-psychotic [24], anticytotoxin [25], and anti-hypertension [26], and insecticidal [27]. In addition, substituted 1,3,4thiadiazole derivatives have received significant attention during the last years, and have been investigated increasingly due to their various therapeutic and industrial applications, the biological activities of 1,3,4-thiadiazole derivatives is supposed due to the presence of =N−C−S− moiety [28,29].…”